1. Field of the Invention
The present invention relates to an animal model for human diseases. More particularly, it relates to a transgenic mouse usable as an animal model for human acquired immunodeficiency syndrome (AIDS).
2. Disclosure of the Related Art
Human immunodeficiency virus (HIV) infection has spread throughout the world since 1981 when a patient with this infection was reported at the first time in the United State, and up to date, persons infected with HIV are presumed to exceed twenty millions. HIV infects human CD4.sup.+ blood cells (i.e., helper T cell and macrophage) predominantly. The HIV infectious disease causes AIDS, which is characterized by decrease in CD4.sup.+ T cells, after the latent period, thereby leading to death; that is, it is a disease that the prognosis is bad. Currently, no effective methods for prevention and treatment (e.g., vaccines) have been established, and the mechanism that HIV causes immunodeficiency has not yet been clarified.
One of the causes that make the solution of those problems late is that there exists no suitable small animal model for HIV infection. Anthropoids such as chimpanzees and monkeys have been utilized as animal models for HIV infection, whereas there are great demands on small animal models for HIV infection due to expensive management cost and limited facility.
Recently, the mouse that human blood cells have been transplanted in a hereditary immunodeficiency mouse (SCID mouse) so that the transplanted human blood cells could be infected with HIV has been developed as an animal model for HIV infection and has been used by some researchers (J. M. McCune et al., Science, 247:564-566, 1990).
However, when this mouse is used as an animal model for HIV infection, human blood cells must be transplanted in every individuals and HIV must be allowed to infect following settlement of the transplanted blood cells, i.e., several weeks after transplantation. Although SCID mouse is used to prevent the graft versus host (GVH) response following transplantation, the settlement of the transplanted human blood cells is insufficient or it does not occur sometimes. Thus, in cases where the SCID mouse is utilized in preparation of animal models for HIV infection, there are problems that preparation of such animal models needs the skill; that traits of individual mice are not constant with reflecting the efficiency of transplantation; and that no immunodeficiency is caused by HIV because HIV does not infect murine lymphocytes.
For the above reasons, there are great demands on small animal models for HIV infection, which are infected with HIV hereditarily; have constant traits; and are able to develop immunodeficiency seen in HIV infected patients.
In this situation, it has been reported in 1996 that when T-cell line tropic HIV strain invades T cells, fusin (or CXCR4) which is a cell surface protein of T lymphocytes is required as well as CD4 which is a other cell surface membrane protein of T lymphocytes (Y. C. Feng et al., Science (Wash. D.C.), 272:872-877, 1996; and J. F. Berson et al., J. Virol., 70:6288-6295, 1996).
The present inventor has continued to study actively in order to solve the above mentioned problems and, as a result, succeeded in production of a transgenic mouse in which at least two human T cell surface proteins are coexpressed on the surface of T lymphocytes of the mouse.